Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies
Sanae Sasaki, … , Harry B. Greenberg, Xiao-Song He
Sanae Sasaki, … , Harry B. Greenberg, Xiao-Song He
Published July 25, 2011
Citation Information: J Clin Invest. 2011;121(8):3109-3119. https://doi.org/10.1172/JCI57834.
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Research Article

Limited efficacy of inactivated influenza vaccine in elderly individuals is associated with decreased production of vaccine-specific antibodies

Abstract

During seasonal influenza epidemics, disease burden is shouldered predominantly by the very young and the elderly. Elderly individuals are particularly affected, in part because vaccine efficacy wanes with age. This has been linked to a reduced ability to induce a robust serum antibody response. Here, we show that this is due to reduced quantities of vaccine-specific antibodies, rather than a lack of antibody avidity or affinity. We measured levels of vaccine-specific plasmablasts by ELISPOT 1 week after immunization of young and elderly adults with inactivated seasonal influenza vaccine. Plasmablast-derived polyclonal antibodies (PPAbs) were generated from bulk-cultured B cells, while recombinant monoclonal antibodies (re-mAbs) were produced from single plasmablasts. The frequency of vaccine-specific plasmablasts and the concentration of PPAbs were lower in the elderly than in young adults, whereas the yields of secreted IgG per plasmablast were not different. Differences were not detected in the overall vaccine-specific avidity or affinity of PPAbs and re-mAbs between the 2 age groups. In contrast, reactivity of the antibodies induced by the inactivated seasonal influenza vaccine toward the 2009 pandemic H1N1 virus, which was not present in the vaccine, was higher in the elderly than in the young. These results indicate that the inferior antibody response to influenza vaccination in the elderly is primarily due to reduced quantities of vaccine-specific antibodies. They also suggest that exposure history affects the cross-reactivity of vaccination-induced antibodies.

Authors

Sanae Sasaki, Meghan Sullivan, Carlos F. Narvaez, Tyson H. Holmes, David Furman, Nai-Ying Zheng, Madhuri Nishtala, Jens Wrammert, Kenneth Smith, Judith A. James, Cornelia L. Dekker, Mark M. Davis, Patrick C. Wilson, Harry B. Greenberg, Xiao-Song He

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Figure 6

Affinity of influenza vaccine virus-specific re-mAbs derived from young and elderly recipients of seasonal TIV.

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Affinity of influenza vaccine virus-specific re-mAbs derived from young ...
Binding affinity was measured by ELISA with microtiter plates coated with individual vaccine component viruses. The binding affinity was defined as the minimum concentration of each re-mAb that resulted in an OD405nm greater than 0.607 in the assay. All re-mAbs (32 from the young group; 43 from the elderly group) with a minimum binding concentration up to 10 μg/ml for 1 of the vaccine component viruses were considered vaccine specific and included for this analysis. The OD405nm threshold of 0.607 was set at a level that would exclude 95% of random control re-mAb as vaccine-specific, based on ELISA results of 48 such re-mAbs derived from individual naive B cells. Geometric means of minimum binding concentrations are shown as bars and numerical values below.